Substance Related Diseases

8/8/2019 Substance Related Diseases

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Opioid -Related Disorders

More than 20 chemically distinct opioid drugs are in clinical use throughout the world. In the

developed countries, the opioid drug must frequently associated with abuse and dependence is

heroina drug that is not used for therapeutic purposes in the United States. Dependence on

opioids other than heroin is seen mostly in persons who have become dependent in the course

of medical treatment, among health care professionals who have easy access to such drugs, and

in those who use drugs that are diverted from medical providers and treatment programs.

Virtually all of the opioid dependence and abuse seen clinically is associated with prototypical

-agonist uploads, and all -agonists produce similar subjective effects. However, the patterns

of use and some aspects of opioid toxicity are powerfully influenced by the route of

administration and the metabolism of the specific opioid, as well as by the social conditions

that determine its price and purity and the sanctions attached to nonmedical use.

DEFINITIONS

The revised fourth edition of theDiagnostic and Statistical Manual of Mental disorders(DSM-

IV-TR) divides opioid-related disorders into disorders (opioid abuse and opioid dependence) and

nine other opioid-induced disorders (e.g., intoxication and withdrawal).

Opioid dependence is a cluster of physiological, behavioral, and cognitive symptoms, which,

taken together, indicate repeated and continuing use of opioid drugs despite significant

problems related to such use.Drug dependence in general has also been defined by the World

Health Organization (WHO) as a syndrome in which the use of a drug or class of drugs takes

on a much higher priority for a given person than other behaviors that once had a higher

value. These brief definitions each have as their central features an emphasis on the drug-

using behavior itself, its maladaptive nature, and on how the choice to engage in that behavior

has shifted and becomes constrained as a result of interaction with the drug over time.

Opioid abuse is a term used to designate a pattern of maladaptive use of an opioid drug leading

to clinically significant impairment or distress

and occurring within a 12-month period, but one in which the symptoms have never met the


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criteria for opioid dependence. The opioid-induced disorders as defined by DSM-IV-TR

include such common phenomena as opioid intoxication, opioid withdrawal, opioid-induced

sleep disorder, and opioid-induced sexual dysfunction. Opioid intoxication delirium is

occasionally seen in hospitalized patients. Opioid-induced psychotic disorder, opioid-induced

mood disorder, and opioid-induced anxiety disorder, by contrast, are quate uncommon with -

agonist opioids but have been seen with certain mixed agonist-antagonist opioids acting at other

receptors. DSM-IY-TR also includes opioid-related disorder not otherwise specifiedfor

situations that do not meet the criteria for any of the opioid-related disorders.

COMPARATIVE NOSOLOGY

The DSM-IV-TR criteria for opioid dependence are the same generic criteria as are applied to

other psychoactive drugs. The notion of a generic concept of dependence is shared with the

tenth revision of theInternational Statistical Classification of Diseases and Related Health

Problems (ICD-10). In the diagnosis of opioid dependence, there generally is a high level of

agreement between DSM-IV-TR and ICD-10: They use similar concepts (the dependence

syndrome varying in degree of severity), although the wording of the criteria for determining

the presence and severity of the syndrome differs. Both require that three elements of the

syndrome occur within a 12-month period.

A major difference between DSM-IV-TR and ICD-10 lies in how sasiv fe&ns& s\fty&a&&.

'dfcw&t.\CXW^ tots mV \>&t ^wt \srrcv abuse. Instead, it includes a category of harmful use that

is substantially different from the concept of abuse in DSM-IV-TR. However, the concept of

harmful use is limited to physical and mental health (e.g., hepatitis, overdose, and skin abscess)

and specifically excludes social impairments. ICD-10 states: "Harmful patterns of use are often

criticized by others and frequently associated with adverse social consequences of various

kinds. The fact that a pattern of use or a particular substance is disapproved of by another

person or by the culture, or may have led to socially negative consequences such as arrest or

marital arguments is not in itself evidence of harmful use."

DSM-IV-TR and ICD-10 also have distinctly different coding systems. ICD-10 separates for

record-keeping purposes mental and behavioral disorders due to use of opioids from those

caused by other categories of drugs. DSM-IV-TR limits the number of distinct drug-induced


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syndromes that can be recorded (except under the categories otherand unspecified) as disorders

induced by opioids.


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ETIOLOGY

Opioid dependence is currently seen as a biopsychosocial disorder in which multiple

factors interact to influence initiation of use, continued use, and relapse after periods of

abstinence.. Those factorspharmacological, social, environmental, personality,

psychopathology, genetic, and familialare the same ones that must be considered

when loocing at abuse and dependence on other categories of drugs. What changes . in the case

of the opioids is the balance of the various factors. For opioids, as for most substances, it is

largely social and cultural factors that influence availability and initial use. In the case of

OPIOIDDRUGS, however, pharmacological factorsthe initial effects and their

consequencesare believed to play important roles in the perpetuation of use and of

progression to dependence. Opioids have potent mood-elevating and euphorigenic actions

in humans and are powerful reinforcers in animal models. This is particularly true when

the effects are rapid in onset, such as when the opioids are injected or inhaled . Perhaps

more than any other category of drugs, the opioids can induce long-lasting alterations in

the nervous system. Some of these changes are responsible for the physical dependence that

causes an aversive withdrawal syndrome when central nervous system (CNS) opioid levels

decline. Other drug-induced changes that may persist for some time after withdrawal include

a hyperresponsiveness to stress and reduced responsivity for ordinary pleasurable events

(hypophoria) It is not clear whether these changes should be considered part of protracted

withdrawalsyndrome or whether they represent distinct phenomena.

DIAGNOSIS AND CLINICAL FEATURES

Opioid Intoxication

DSM-IV-TR Diagnostic Criteria for Opioid intoxication


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A. Recent use of an opioid.

B. Clinically significant maladaptive behavioral or psychological

changes (e.g., initial euphoria followed by apathy dysphoria,

psychomotor agitation or retardation, impaired judgment, or

impaired social or occupational functioning) that developed during

, or shortly after, opioid use.

C. Pupillary constriction (or pupillary dilation due to anoxia from

severe overdose) and one (or more) of the following sings, developing

during, or shortly after, opioid use:

(1) Drowsiness or coma

(2) Slurred speech

(3) Impairment in attention or memory

D. The symptoms are not due to a general medical condition are

not better accounted for by another mental disorder

Specifyif:

With perceptual disturbances.

Opioid Withdrawal

The opioid withdrawal syndrome can vary greatly in intensity, depending primarily on

the level of physical dependence (i.e., the chronic dose of the opioid used), the degree to

which the opioid effects on the CNS were continuously exerted, the duration of use, and the

rate at which the opioid is removed from the receptors. These generalizations appear to

apply as well to other categories of drugs, such as barbiturates and benzodiazepines. The

DSM-IV-TR diagnostic criteria for opioid withdrawal are shown in

Although there are numerous signs and symptoms associated with opioid withdrawal, not

all are uniformly present across withdrawal episodesthere can be considerable variability

between persons in the particular cluster of symptoms exhibited during opioid withdrawal.


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DSM-IV-TR Diagnostic Criteria for Opioid Withdrawal

A. Either of the following:

(1) Cessation of (or reduction in) opioid use that has been heavy

and prolonged (several weeks or longer).

(2) Administration of an opioid antagonist after a period of opioid

use.

B. Three (or more) of the following, developing within minutes to

several days after Criterion A:

(1) Dysphoric mood

(2) Nausea or vomiting

(3) Muscle aches

(4) Lacrimation or rhinorrhea

(5) Pupillary dilation, piloerection, or sweating

(6) Diarrhea

(7) Yawning

(8) Fever

(9) Insomnia

C. The symptoms in Criterion B cause clinically significant distress or

impairment in social, occupational, or other important areas of

functioning.

D. The symptoms in Criterion are not due to a general medical condition

and are not better accounted for by another mental disorder

Opioid Abuse and Opioid Dependence

Opioid abuse is a pattern of maladaptive use of an opioid drug leading to clinically significant


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impairment or distress and occurring within a 12-month period, but one in which the

symptoms have never met the criteria for opioid dependence.

Opioid dependence is inferred from behaviors that indicate some decrease in volitional

control over the use of an opioid drug. DSM-IV-TR specifies the criteria to be used by the

clinician to decide whether the patient exhibits such a decrease in volitional control. These

criteria are not specific for opioids but are believed to apply for all psychoactive agents. DSM-

IV-TR does not require that any single criterion be met, and none is given special weight.

Thus, the presence of tolerance and physical dependence (withdrawal) is not required.

However, according to DSM-IV-TR, if tolerance and physical dependence are present, they

should be noted specifically. Because tolerance develops to many of the actions of opioid

drugs after long-term use, opioid effects are not readily detected by even the careful observer.

Patients maintained on large oral doses of methadone function quite normally. Physicians,

nurses, and other medical personnel who use opioids, even by injection, may go undetected by

their colleagues for months or years. Thus, a candid history obtained from the patient or a

reliable informant is needed to make a diagnosis of dependence, although evidence of recent

and long-term use can be developed by testing urine or hair for the presence of opioids.

Opioid Intoxication Delirium

Opioid intoxication delirium is most likely to happen when opioids are used in high doses,

are mixed with other psychoactive compounds, or are used by a person

with preexisting brain damage. Certain opioids, such as meperidine, have toxic metabolites

that can accumulate, causing delirium and sometimes causing seizures. Impaired renal

function increases the likelihood of accumulation.

Opioid-lnduced Psychotic Disorder

Opioid-induced psychotic disorder can begin during opioid intoxication. The DSM-IV-TR

diagnostic criteria are contained in the section on schizophrenia and other psychotic disorders.

Clinicians can specify whether hallucinations or delusions are the predominant symptoms and

whether the onset occurs during intoxication or withdrawal.

Opioid-induced Mood Disorder

Opioid-induced mood disorder can begin during opioid intoxication or withdrawal and can


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result from chronic use. Opioid-induced mood disorder symptoms may be of a manic,

depressed, or mixed nature. A person coming to psychiatric attention with opioid-induced mood

disorder usually has mixed symptoms, combining irritability, expan-siveness, and depression.

Some degree of depressed mood (hypophoria) typically occurs during and for several weeks

after opioid withdrawal. Opioid-induced mood disorder should not be diagnosed after opioid

withdrawal unless the severity of mood disturbance exceeds what is normally encountered or

persists for more than a few weeks and is of sufficient intensity to warrant independent clinical

attention

Opioid-induced Sleep Disorder and Opioid-induced Sexual Dysfunction

Opioid-induced sleep disorder and opioid-induced sexual dysfunction are diagnostic categories

in DSM-IV-TR. Hypersomnia is likely to be a more common sleep disorder among those

given opioids therapeutically, but disturbed sleep (insomnia) is a common complaint of patients

maintained on opioid agonists such as methadone. The most common sexual dysfunction is

likely to be impotence, but patients maintained on methadone may complain of inability to

achieve orgasm, rather than impotence

Opioid-Related Disorder Not Otherwise Specified

DSM-IV-TR includes diagnoses for opioid-related disorders with symptoms of delirium,

abnormal mood, psychosis, abnormal sleep, and sexual dysfunction. Clinical situations that do

not fit into these categories are examples of appropriate cases for the use of the DSM-IV-TR

diagnosis of opioid-related disorder not otherwise specified

DSM-IV-TR Diagnostic Criteria for Opioid-Related

Disorder Not Otherwise Specified

The opioid-related disorder not otherwise specified category is for

disorders associated with the use of opioids that are not

classifiable as opioid dependence, opioid abuse, opioid

intoxication, opioid withdrawal, opioid intoxication delirium,

opioid-induced psychotic disorder, opioid-induced mood disorder,

opioid-induced sexual dysfunction, or opioid-induced sleep

disorder.


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PATHOLOGY AND LABORATORY EXAMINATION

In opioid abuse and opioid dependence, there may be no abnormal laboratory findings at all.

Standard urine tests for heroin actually test for its main metabolite, morphine, and can usually

detect morphine (heroin) for 12 to 36 hours after use. A urine test that is positive for morphine

can also be caused by therapeutic doses of codeine or by the ingestion of modest amounts of

poppy seeds (of the type and amount used to flavor bagels and other breads and pastries).

Potent opioids, such as fentanyl (Actiq), may not be detected by standard opioid urine screens.

If it is suspected that a specific opioid is being abused, it can be useful to check with a

laboratory to ensure that the proper urine test is obtained, as not all opioids react with the test

for morphine (e.g., methadone). Opioids with longer half-lives, such as methadone, may be

detected for longer periods (4 or more days in the case of methadone) on a urine screen that

tests specifically for such medications. Analysis of hair samples can provide information on

drug use over the preceding 2 to 3 months. Samples of oral fluids can detect recent opioid use

with approximately the same sensitivity as urine testing.

Persons who have shared injection implements often test positive for hepatitis (B and C) and

for HIV. Liver enzyme tests may be elevated if there is active hepatitis. There may be

positive and false-positive tests for syphilis. Chest X-rays may show evidence of

pulmonary fibrosis if the person has been using injection materials contaminated with

microcrystalline talc or cotton particulates. During withdrawal, white blood cell counts and

Cortisol levels may be elevated. Physical findings may be unremarkable if opioids are

ingested orally; snorting (insufflation) of heroin may irritate nasal membranes. Drug

injectors, however, may show widespread evidence of having used unsterile injection

equipment. There may be needle tracks over veins on the arms, legs, and, in some cases, the

backs of the hands and the femoral and jugular veins. Infections and venous scleroses and

lymph obstruction may lead to severe edema of the hands and feet. There may be skin

abscesses or scars on accessible skin surfaces as a result of unsterile subcutaneous injections

(Fig. 11.10-3). There may be rock-like hardening of subcutaneous and muscle tissue as a

result of repeated IM injections of meperidine (often seen among health professionals).

Endocarditis may produce fever and heart murmurs. In addition, a variety of neurological

sequelae of IV heroin use may be detected.

TREATMENT


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Treatment of Opioid Intoxication (Overdose)

Overdose with an opioid agonist can produce respiratory depression and is therefore a

medical emergency. The first task is to ensure an adequate airway. Tracheopharyngeal

secretions should be aspirated; an airway may be inserted. The patient should be ventilated

mechanically until an opioid antagonist can be administered. There are two approved opioid

antagonists (naloxone, nalmefene [Revex]) that can be administered parenterally for reversal of

an opioid overdose. Naloxone has a relatively short half-life (60 to 90 minutes) and must be

repeatedly administered in patients who have overdosed on an opioid with a longer half-life

(e.g., methadone). Initial IV naloxone dosing is approximately 0.8 mg per 70 kg of body

weight. Signs of improvementincrease in respiratory rate and pupillary dilation should

occur promptly. If there is no response to the initial dosage, naloxone may be repeated after

intervals of a few minutes. Nalmefene has a longer duration of action (its half-life is

approximately 10 hours), anda single dose of nalmefene may be sufficient to produce sustained

reversal for the duration of the effects of the opioid agonist overdose. Nalmefene's onset of

effects typically occurs within minutes after IV administration, and the usual initial dose is 0.5

to 1.0 mg.

In opioid-dependent patients, too much naloxone or nalmefene may produce signs of

withdrawal (precipitated opioid withdrawal), as well as reversal of overdosage. In some

instances, patients may become agitated owing to precipitated withdrawal symptoms. A relative

advantage of naloxone is that precipitated withdrawal effectsif they occurare of relatively

short duration. In contrast, nalmefene-precipitated withdrawal can last for hours.

In the past, it was thought that, if no response was observed after administering naloxone or

nalmefene, then CNS depression was probably not solely due to opioids. However,

buprenorphine is difficult to reverse with opioid antagonists, and higher doses of naloxone and

nalmefene may be required for an overdose of buprenorphine. (However, the risk of respiratory

depression from an overdose of buprenorphine is uncommon, as reviewed later in this chapter.


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Cocaine-Related Disorders

Few public health issues attracted as much media attention in the United States during the

1980s and early 1990s as the problems resulting from the use of cocaine and "crack."Although the intranasal use of cocaine hydrochloride in the early 1980s was associated with

high-income, "jet-set" users, smokable "crack cocaine has become an endemic drug

problem in the inner cities across the United States. Epidemiological evidence has

documented that the peak of this epidemic has passed in the United States, but available data

indicate that rates of cocaine use are increasing in a number of European countries.

There is a wealth of new information on the neurobiology of cocaine and cocaine

dependence, treatment research efforts have been extensive, and progress has been made in

identifying behavioral-psychosocial treatments. However, in spite of well-funded research,

there are still no clinically useful pharmacotherapies for the treatment of cocaine-related

disorders.

DEFENITIONS

Substance use may be associated with a number of distinct disorders, of which _dependence

and abuse are but two. In the case of cocaine, the revised fourth edition of the Diagnostic and

Statistical Manual of Mental Disorders (DSM-IV-TR) describes ten other substance-related

disorders. Cocaine dependence is defined in DSM-IV-TR as a cluster of physiological ,

behavioral, and cognitive symptoms that, taken

Together, indicate that the person continues to use cocaine despite significantproblems related to such use. With cocaine dependence, individuals find

it increasingly difficult to resist using cocaine whenever it

is a available. It is defined in the tenth revision of theInternational Statistical

Classification of Diseases and Related Health Problems (ICD-10) as a

cluster of physiological, behavioral, and cognitive phenomena

in which the use of cocaine takes on a much higher priority for a given .individual than do other

behaviors that once had a greater value. Central

to these definitions is the emphasis placed on the drug-using


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behavior, its maladaptive nature, and how, over time, the voluntary

choice to engage in that behavior shifts and becomes constrained as a result of

interactions with the drug..

Cocaine abuse is a term used in DSM-IV-TR to categorize a pattern of

maladaptive cocaine use leading to clinically significant impairment or distress within a

12-month period but one in which the symptoms have not met criteria for cocaine

dependence. Specifically, when there is evidence of tolerance, withdrawal, or compulsive

behavior associated with obtaining or administering cocaine, a diagnosis of dependence

rather than abuse should be used. ICD-10 does not use the term.

Other cocaine-related disorders include cocaine intoxication, .cocaine

withdrawal, cocaine-induced psychotic disorder with delusions or with hallucinations,

cocaine intoxication delirium, cocaine -induced mood disorder, cocaine-induced anxiety

disorder, cocaine-induced sleep disorder, cocaine-induced sexual dysfunction, and cocaine-

related disorder not otherwise specified. The DSM-IV-TR coding scheme provides distinct

code numbers for cocaine dependence and cocaine abuse.

DSM-IV-TR Cocaine-Related Disorders

Cocaine use disorders Cocaine dependence

Cocaine abuse Cocaine-induced disorders

Cocaine intoxication Specifyif:

With perceptual disturbances Cocaine withdrawal Cocaine

intoxication delirium Cocaine-induced psychotic disorder

with delusions Specifyif:

With onset during intoxication

Cocaine-induced psychotic disorder with hallucinations

Specifyif:

With onset during intoxication Cocaine-induced

mood disorderSpecifyif:

With onset during intoxication With onset during

withdrawal Cocaine-induced anxiety disorder

Specifyif:


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With onset during intoxication With onset during

withdrawal Cocaine-induced sexual dysfunction

Specifyif:

With onset during intoxication Cocaine-induced

sleep disorderSpecifyif:

With onset during intoxication With onset during withdrawal

Cocaine-related disorder not otherwise specified

ETIOLOGY

Substance dependence is currently viewed as the result of a process

In which social, psychological, cultural, and biological factors influence substance

-using behavior. The actions of the drug are seen as

critical, but is recognized that not everyone who becomes dependent

experiences the effects of a given drug in the same way. Further,

depending on the individual, different factors may be more or less

important at deferent stages of the process, even with the same class

of pharmacological agents.

Social and cultural factors largely influence the availability and initial use of cocaine and other

substances. In the case of cocaine, pharmacological factors are believed important in

perpetuating useand progression to dependence. Cocaine has potent mood-elevating and

euphorigenic actions, especially when its effects have rapid onset, as when cocaine is

injected or inhaled. Although some physical dependence develops, a physically

uncomfortable, aversive withdrawal syndrome probably is less prominent in perpetuating

cocaine use than that of opioids and sedatives.

Comorbidity Additional psychiatric diagnoses are quite common among cocaine-

dependent patients. It is not always evident how this comorbidity is linked etiologically to

cocaine, but the epidemiological evidence clearly shows that the presence of a psychiatric

disorder not related to substance abuse (e.g., mood disorders, schizophrenia, and antisocial

personality disorder) substantially increases the odds of developing substance abuse and

dependence. For some people, cocaine may serve to alleviate various psychiatric disorders or


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dysfunctional states. Some users, for example, may find relief from dysthymic disorder. Others

may find that cocaine facilitates sexual activity, permits extended socializing, or counteracts

the sedative effects of alcohol. However, although factors may explain substance use on

more than one occasion, they do not account for progression to dependence or abuse.

Genetic Factors The most convincing evidence to date of a genetic influence on cocaine

dependence comes from studies of twins, ale twins. A study of male who served in the U.S.

military between 1965 and 1975 found higher concordance rates for stimulant dependence

( cocaine, amphetamines, and amphetamine-like drugs) among monozygotic than

dizygotic twins. The analyses indicated that genetic factors and unique (unshared)

environmental factors contributed approximately equally to the development of stimulant

dependence. A study of male twins in Virginia found a common genetic factor exerted a strong

influence on risk for illicit use and abuse/dependence for six distinct classes of drugs.

Environmental factors were the major determinant of whether a particular class of drugs are

used by predisposed individuals. Other studies have shown genetic contributions to attention- deficit/

hyperactivity disorder (ADHD), conduct disorder, and antisocial personality disorder. Because

these disorders are important riski drug use and dependence, these findings also support

genetic involvement in the etiology of drug dependence in general.

In animal models, it is interesting to note that laboratory animal _strains differ greatly in

their willingness to self-administer psychoactive drugs including cocaine, and that strains

that differ even more markedly can be developed.

Other Factors Social, cultural, and economic factors are powerful

determinants of initial use, continuing use, and relapse. Excessive use is far more likely in

countries in which cocaine is readily available.

Different economic opportunities may influence certain groups more

than others to engage in selling illicit drugs, and selling is more likely to be carried out in

familiar communities than in those in which the seller runs a high risk of arrest.

Because in both human and animal studies alternative positive

reinforcers compete with drugs as reinforcers, the absence of such

nondrug alternatives can be seen as a causal factor for use, especially

when drugs are available and the social pressures against using them

are not strong. Alternative positive reinforcers are not limited to


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material rewards but include psychological rewards associated with

satisfying interpersonal relationships and the self-esteem that derives

from achievements in socially acceptable roles. In animal models,

chronic stress mediated by high levels of Cortisol increases sensitivity to the reinforcing effects

of cocaine and induces relapse to drug self-administration in withdrawn animals.

DIAGNOSIS AND CLINICAL FEATURES

Patterns of Use and Abuse

Vhere are several patterns of cocaine use and abuse. For example, the indigenous people of the

Andes chew coca leaves daily, but apparently very few progress to excessive use or toxicity.

Although some people can use cocaine intermittently without becoming dependent, it is not

clear how long such intermittent, nondependent use can continue and for what proportion of

users. Cocaine use that does not cause problems for the user does not meet the DSM-IV-TR

criteria for either dependence or abuse.

Among people seeking treatment for cocaine dependence (unlike opioid dependence), daily

use of the drug is not the most common pattern. Instead, use may be intermittent. Intermittent

use consists of episodes or binges of use, often starting on weekends and paydays and lasting

until the drug supply is exhausted or toxicity develops The runs, or binges, during which the

drug may be used every 15 to 30 minutes, can last 7 or more consecutive days but typically are

shorter. Although there appears to be little tolerance between binges, changes in the response

to the drug occur during the binge. Euphoric effects seem less prominent, and anxiety, fatigue,

irritability, and depression increase. Any pause in the drug use causes blood concentrations to

drop; typically, there is dysphoria rather than a return to normal mood. If cocaine is stillavailable, it is used to dispel the dysphoria. When the binge is interrupted or supplies have

been depleted, a cocaine "crash" quickly follows. Patients report the sense of needing more

cocaine to get the same effect (tolerance) more commonly than the experience of pronounced

withdrawal. Some users distinguish between a brief crash and withdrawal. A substantial

proportion of cocaine users seeking treatment report daily or almost daily use, often associated

with daily heroin use. A small percentage

of patients report using high doses for a few days a month over a long period; such people

may still meet the criteria for dependence.


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In the early stages, cocaine use may cause little interference with normal activities. Some

people may even find that the sense of energy and heightened sense of self-confidence facilitate

productive activity. Others may find that the cocaine facilitates social interaction, particularly

enhancing sexual arousal and enjoyment, at least initially. The development of sexual dysfunction

later in the course of use is better documented than is the enhancement.

In addition to feelings of euphoria, cocaine use may also induce concurrent feelings of anxiety,

irritability, and suspiciousness. Users may commit crimes to obtain money to buy cocaine, and

such crimes may involve violence. In addition, cocaine can induce paranoid ideation, and there are

reports of homicide and attempted homicide during such cocaine-induced toxic states.

Cocaine abusers frequently use sedatives or opioids to modulate the stimulant and toxic effects

of the cocaine, a practice that can lead to concurrent dependence on sedatives or opioids.

Sometimes an opiate, such as heroin, and cocaine are injected intravenously simultaneously; the

mixture (speedball) is reportedly especially euphorigenic. Similar synergistic effects are seen

when cocaine and buprenorphine (Buprenex, Subutex) are taken simultaneously. Alcohol is

probably the substance most commonly used in conjunction with cocaine, and its use may

become associated with cocaine use and can trigger cocaine craving in former users trying to

abstain from cocaine.


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Cocaine Dependence As drug use progresses, greater priority is often given to

obtaining and using cocaine than to meeting other social obligations or avoiding toxicity or

arrest. The user may engage in illegal activities to raise money for cocaine or trade sex for it.

At this stage, the use of cocaine is considered maladaptive and probably meets the DSM-IV-

TR criteria for cocaine abuse or dependence. The DSM-IV-TR criteria for cocaine

dependence are the same generic criteria applied to other substances (Table 11.1-3). A

diagnosis of dependence requires a maladaptive drug use pattern that leads to clinically

significant impairment or distress, as indicated by at least three of seven criteria presented in

the table. DSM-IV-TR instructs the clinician to specify whether physiological dependence is

present (i.e., evidence of either tolerance or withdrawal as defined in the diagnostic criteria).

Drug use to prevent withdrawal is not as dominant with cocaine dependence as with opioid

dependence. However, the other criteria for dependence are common among heavy users of

cocaine. Tolerance to some drug actions (e.g., euphorigenic effects) can coexist with

increased sensitization to other actions (e.g. anxiogenetic and psychotogenic effects).

Cocaine Abuse Some cocaine users developproblems or adverse effects related to their

drug use (i.e., their maladaptive) even though such use does not meet the three-criteria

requirement for the diagnosis of dependence. Examples of such recurrent maladaptive

patterns include use that leads to multiple legal problems ; inability to meet major social,

school, or work-related obligations; and continued use despite social or vocational

difficulties caused by, or aggravated by, cocaine use. When one more such substance-

related problems occur in a 12-month period, but the pattern has never met the criteria for

dependence, the diagnosis of cocaine abuse (Table 11.1-8) should be made.

Cocaine Intoxication Delirium and cocaine-Induced Psychotic Disorder

Whereas some paranoia or

hypervigilance is typical of cocaine intoxication, and tactile and other hallucinations may also

occur, cocaine use can also induce a toxic delirium and a more persistent toxic psychotic

disorder characterized by suspiciousness, paranoia, visual and tactile hallucinations, and loss of


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insight. The hallucination of bugs (cocaine bugs) or vermin crawling under the skin

(formication) is sometimes reported and is often with associated excoriation of the skin. A

paranoid syndrome can develop within 24 hours after the beginning of a cocaine binge. When

the syndrome develops in the presence of a clear sensorium, and the person retains insight into

the drug-induced nature of the symptoms, it is called cocaineintoxication, even when there arehallucinations. When insight is lost, but the sensorium is clear, the syndrome is called cocaine-

induced psychotic disorder with delusions orwith hallucinations. If consciousness is disturbed

(i.e., the ability to focus, sustain, or shift attention is reduced), and deficits in memory and

orientation exits, the diagnosis is cocaine intoxication delirium.

Cocaine Intoxication

A. Recent use of cocaine,

B. Clinically significant maladaptive behavioral or psychological

e.g., euphoria or affective blunting; changes in sociability ; hypervigilance;

interpersonal sensitivity; anxiety, tension, or anger; stereotyped behaviors; impaired

judgment; or impaired social or occupational functioning) that developed during, or

shortly after, use of cocaine.

C. Two (or more ) of the following, developing during, or shortly after cocaine

use:

(1) Tahycardia or bradycardia

(2) Pupillarydilation

(3) Elevantedor lowered blood pressure

(4) Perspiration or chills

(5) Nauseaor vomiting

(6) Evidence of weight loss

(7) Psychomotor agitation or retardation

(8) Muscular weakness, respiratory depression, chest pain, or cardiac atrhythmias

(9) Confusion, seizures, dyskinesias, dystonias, or coma


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D. The symptoms are not due to a general medical condition and are not better

accounted for by another mental disorder.

Specify if:

With perceptual disturbances

.

Cocaine Withdrawal Cocaine withdrawal phenomena have not been as thoroughly studied

as those associated with opioids or alcohol. No experimental studies have been conducted in

which patient with known baseline characteristics have been stabilized solely on large

doses of cocaine and then abruptly withdrawn. Consequently, most data have been derived from

interviews and patients' recollections or from observations of hospitalized patients whose

level of drug ingestion and prior baseline characteristics can only be estimated. During the

cocaine epidemic of the 1980s, approximately 50 percent of cocaine users reported

experiencing some type of withdrawal when drug use was interrupted.

An early description of withdrawal based on interviews of outpatients described a three-phase

syndrome in which the first phase, the crash, was characterized by agitation, depression,anorexia, and high cocaine craving. This cluster of symptoms was followed by a decrease

in cocaine craving, fatigue, depression, and a desire for sleep, followed in turn by

exhaustion and hypersomnia, with intermittent awakening, and hyperphagia. The second

phase was reported to be heralded by normalized sleep, improved mood, and low levels of

craving, but that relatively benign phase was succeeded by a return of anergia, anhedonia,

anxiety, and increased cocaine craving, especially in response to stimuli previously associatedwith cocaine use. A third phase, extinction (which appears to represent a period of extended

vulnerability to relapse rather than a phase of an extended withdrawal syndrome) was also

described.

Others who have observed cocaine-dependent patients admitted to clinical and research

units have not reported seeing such a complex phasic withdrawal. Instead, symptoms of

depression and craving for cocaine declined steadily over several weeks. After 3 weeks, sleep,

weight, and appetite were mostly comparable to those of normal controls on the same unit.


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Hypersomnia, disturbed sleep, hyperphagia, and excessive weight gain were not seen, nor

was a severe crash observed. The phases and fluctuations in craving previously reported

might have been related to environmental stimuli, j

Some of the inconsistencies in the findings and symptoms associated with cocaine cessation

are probably attributable to differences in the dose and duration of use and to vulnerability

factors. In interviews with almost 400 cocaine abusers, including approximately 100 who

were not seeking treatment, some 83 percent reported tolerance to cocaine effects (needing

more to get the same effect), and 52 percent reported having undergone some type of

withdrawal. Those seeking treatment were more likely to report experiencing withdrawal.

Available data show no convincing evidence that a protracted cocaine withdrawal syndrome

follows resolution of the signs and symptoms associated with abrupt cessation. However,

abnormalities of brain function appear to persist for at least 12 weeks, and, possibly, subtle

withdrawal phenomena increase vulnerability to relapse.

Although not commonly observed during recent clinical studies, severe depression,

sometimes associated with suicidal ideation, is reported in the older literature on cocaine

withdrawal and in occasional contemporary clinical reports. Emil Erlenmeyer reported in

1886 that depression was likely to be seen when cocaine was stopped. Maier(Der

Kokainismus, 1926) noted that depression and apathy appeared on cessation of cocaine. To

what degree the more severe depressive features are a part of withdrawal or represent the

emergence of primary mood disorder is unclear.

vjhe DSM-IV-TR diagnostic criteria for cocaine withdrawal (Table 11.6-3) specify that the

syndrome follows the cessation (or reduction) of heavy, prolonged cocaine use. Further, the

dysphoric mood and other symptoms (e.g., fatigue and sleep disturbances) must be intense

enough to cause significant distress or impairment. Thus, the criteria are structured so that the

brief dysphoria and fatigue (crash) that follow a single short binge by an occasional user do not

lead to a diagnosis of withdrawal. Drug craving, often a part of cocaine withdrawal, is not

included among DSM-IV-TR diagnostic criteria.

Table 11.6-3

DSM-IV-TR Diagnostic Criteria for Cocaine Withdrawal


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A. Cessation of (or reduction in) cocaine use that has been heavy

and prolonged.

B. Dysphoric mood and two (or more) of the following physiological

changes, developing within a few hours to several days after Cri

terion A:

(1)Fatigue

(2) Vivid, unpleasant dreams /

(3) Insomnia or hypersomnia

(4) Increased appetite

(5) Psychomotor retardation or agitation

C. The symptoms in Criterion B cause clinically significant distress

or impairment in social, occupational, or other important areas of

functioning.

D. The symptoms are not due to a general medical condition and are

not better accounted for by another mental disorder.

er Cocaine-Induced Disorders Other psychiatric syndromes that may develop in the

se of cocaine use include cocaine-induced mood disorder, cocaine-induced anxiety disorder,

cocaine-induced sleep disorder. With each of those disorders, the clinician should specify whether

onset occurred during intoxication or during withdrawal. DSM-IV-TR also describes cocaine-

ced sexual dysfunction and a category of cocaine-related disorder not otherwise specified.

aine-induced mood disorder can occur during use, intoxication, or withdrawal. During use and

xication, the disorder is more likely to simulate a manic, hypomanic, or mixed episode; during

rawal, it is more likely to involve a depressed mood. Such diagnoses are difficult to make during

ds of active drug use or during the first week or two of withdrawal. Because sexual dysfunction,

nxiety, and disturbed sleep are seen so commonly during cocaine use and withdrawal, the

noses should be made only when the disturbances or dysfunctions are judged to be in excess of

t usually associated with intoxication and withdrawal and only when severe enough to require

ependent treatment or attention. Panic episodes that develop during cocaine use may persist for

ny months after cessation. Lasting vulnerability to panic attacks may be linked to sensitization


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phenomena.

TREATMENT

Selection of Treatment Setting

ral principles of treatment for cocaine dependence do not differ much from those for other

s of drug dependence. Patient heterogeneity requires careful assessment of the patient and

ful selection among alternative treatment approaches. Cocaine dependence severe enough to

formal treatment is often associated with other psychiatric diagnoses. Not all cocaine users

extensive treatment; some who are not severely dependent respond to external pressures, as

mployers insist on carefully monitoring substance use. Among the factors influencing selection

SEVERITY of dependence, other drugs being used concurrently, comorbid medical and

tric disorders, and the preferences of the patient and the alternatives available. Availability, in

often influenced by the policies of managed care companies, the patient's resources, and

s of therapy provided locally.

the few reliable predictors of treatment response number of cocaine use days within the past

e time of treatment admission and route of cocaine administration. There is considerable

ce that individuals who use cocaine on a daily or near-daily frequency or use cocaine by the

n route, or both, are more difficult to engage in outpatient treatments, are retained in treatment

rter durations, and have poorer outcomes. These data suggest that the use of more intensive

nt (e. g. residential or inpatient settings) is preferable for individuals with these pretreatment

files.

In general, treatment can be initiated in intensive outpatient settings, although often third-

party payers do not authorize and public sector programs cannot provide the duration of

treatment or the intensity shown to be most effective. Research on treatment outcome has

consistently demonstrated that individuals who are retained inoutpatient treatments for

longer durations (typically 90 days or more) have better outcome than those who are

retained for shorter durations. In addition, in a prospective study in which cocaine-

dependent individuals were randomly assigned to to receive 30 days or 120 days of thrice-

weekly, manualized outpatient treatment, there was a significantly superior outcome

associated with the longer treatment episode. A study using random assignment found that at

4 months, working-class veterans treated in a day hospital program were about as successful


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in reducing their cocaine use and improving social functioning as those treated in a 28-day

inpatient program. However, a somewhat higher proportion of those assigned to the inpatient

setting completed the 28-day program. Currently, severe depression with suicidal ideation,

psychosis, or substance use that has repeatedly failed to respond to outpatient efforts are the

indications for hospitalization. A retrospective study of individuals treated : for cocaine

dependence in various settings found no advantage in outcome for inpatient treatment lasting

more than 2 weeks.

In many instances, neither the patient nor the c selection of the setting and type of

treatment. Patients are often referred (mandated) to treatment by the criminal justice often

prefers long-term residential programs (therapeutic). The intensity and specificity of servicesfor panics (i.e., medical, psychiatric, and vocational) are now considered determinants of

outcome in the specific problem areas.

Detoxification The cocaine withdrawal syndrom is distinct from the opioid, alcohol, or sedative-hypnotic withdrawal syndrome

in that there are no physiological disturbances that necessitate inpatient or residential drug withdrawal. Thus, it is generally

possible to engage in a therapeutic trial of outpatient withdrawal before deciding whether a more intensive or controlled setting is

required forpatients unable to stop without help in limiting their access to cocaine. Patients withdrawing from cocaine typically

experience fatigue, dysphoria, disturbed sleep, and some craving; some may experience depression. No pharmacological agents

reliably reduce the intensity of withdrawal, but recovery over a week or two is generally uneventful. It may take longer, however,

for sleep, mood, and cognitive function to recover fully.

Substance Related Diseases

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